Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia

2001 ◽  
Vol 91 (3) ◽  
pp. 1176-1184 ◽  
Author(s):  
I. Mark Olfert ◽  
Ellen C. Breen ◽  
Odile Mathieu-Costello ◽  
Peter D. Wagner
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Exercise Training ◽  
Absolute Intensity ◽  
Mrna Levels ◽  
Rat Skeletal Muscle ◽  
Vegf Mrna ◽  
Hypoxic Training ◽  
Response To Exercise

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O2 fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-β1, and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA ( P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P< 0.05), absent TGF-β1 and flt-1 mRNA responses to exercise, and an approximately threefold ( P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle

2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
Author(s):  
Lotte Jensen ◽  
Henriette Pilegaard ◽  
P. Darrell Neufer ◽  
Ylva Hellsten
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Splice Variants ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.

Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise

1999 ◽  
Vol 277 (6) ◽  
pp. H2247-H2252 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
R. Henry ◽  
E. A. Noyszewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Acute Exercise ◽  
Work Rate ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular[Formula: see text] has been proposed as a stimulus for this process. Thus we studied muscle cell[Formula: see text] [myoglobin[Formula: see text]([Formula: see text])] during exercise in normoxia and in hypoxia (12% O2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 ± 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 ± 6.7 or 7.1 ± 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in[Formula: see text] in hypoxia (3.8 ± 0.3 mmHg) compared with normoxia (7.2 ± 0.6 mmHg) but failed to reveal a relationship between [Formula: see text] during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular [Formula: see text]as a stimulus for this response.

Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise

2000 ◽  
Vol 88 (4) ◽  
pp. 1192-1198 ◽  
Author(s):  
Timothy P. Gavin ◽  
David A. Spector ◽  
Harrieth Wagner ◽  
Ellen C. Breen ◽  
Peter D. Wagner
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Methyl Ester ◽  
Acute Exercise ◽  
Transforming Growth Factor ◽  
No Production ◽  
Vegf Mrna ◽  
Exercise Induced ◽  
Response To Exercise

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-β1 (TGF-β1) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF-β1 gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups ( n = 6 each): 1) saline + rest, 2) saline + exercise, 3) 30 mg/kg N ω-nitro-l-arginine methyl ester (l-NAME, a known NOS inhibitor) + rest, 4) 30 mg/kgl-NAME + exercise, 5) 300 mg/kg l-NAME + rest, 6) 300 mg/kg l-NAME + exercise, 7) 300 mg/kg N ω-nitro-d-arginine methyl ester (d-NAME, inactive enantiomer of l-NAME) + rest, and 8) 300 mg/kg d-NAME + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10° incline. VEGF, TGF-β1, and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF-β1 mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated ∼50% by 30 and 300 mg/kgl-NAME; the TGF-β1 mRNA increase was unaffected by 300 mg/kg l-NAME. In addition, 300 mg/kgd-NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg l-NAME had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life.

VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle

1995 ◽  
Vol 269 (5) ◽  
pp. H1827-H1831 ◽  
Author(s):  
J. Hang ◽  
L. Kong ◽  
J. W. Gu ◽  
T. H. Adair
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Motor Nerve ◽  
Physiological Role ◽  
Northern Analysis ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna

Vascular endothelial growth factor (VEGF; also called vascular permeability factor) is a secreted mitogen with distinct target cell specificity for vascular endothelial cells. Hypoxia upregulates VEGF expression, making it a likely mediator of the angiogenesis that occurs in poorly perfused tissues. The purpose of this study was to determine whether VEGF gene expression is upregulated in chronically stimulated skeletal muscles, where hypoxia is thought to trigger the growth of blood vessels. The right anterior tibialis and extensor digitorum longus muscles of 12 rats were stimulated electrically (10 Hz, 300 microseconds pulses) for up to 21 days by way of the peroneal motor nerve. The contralateral muscles served as control. Northern analysis showed that VEGF mRNA levels increased by approximately sixfold after 4 days of stimulation and then decreased gradually over the next several days. VEGF mRNA levels were still elevated by two- to threefold after 21 days of stimulation. Higher VEGF mRNA levels in the early stages of muscle stimulation and gradually decreasing levels in later stages are consistent with a metabolic hypothesis in which tissue oxygenation controls VEGF expression. These studies support the hypothesis that VEGF has a physiological role in promoting angiogenesis in stimulated skeletal muscle.

Effect of short-term exercise training on angiogenic growth factor gene responses in rats

2001 ◽  
Vol 90 (4) ◽  
pp. 1219-1226 ◽  
Author(s):  
Timothy P. Gavin ◽  
Peter D. Wagner
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Exercise Training ◽  
Citrate Synthase ◽  
Short Term ◽  
Vegf Mrna ◽  
Oxidative Potential ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Exercise Induced

We investigated whether 1) 5 days of exercise training would reduce the acute exercise-induced increase in skeletal muscle growth factor gene expression; and 2) reductions in the increase in growth factor gene expression in response to short-term exercise training would be coincident with increases in skeletal muscle oxidative potential. Female Wistar rats were used. Six groups (rest; exercise for 1–5 consecutive days) were used to measure the growth factor response through the early phases of an exercise training program. Vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Citrate synthase activity was analyzed from the right gastrocnemius. VEGF and TGF-β1 mRNA increased after each of 5 days of exercise training, whereas exercise on any day did not increase bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on days 2–5. However, the reduced increase in VEGF mRNA observed on days 2–5 was not coincident with increases in citrate synthase activity. These findings suggest that, in skeletal muscle, 1) VEGF and TGF-β1 mRNA are increased through 5 days of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA responses on days 2–5 does not result from increases in oxidative potential.

scholarly journals Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content

2011 ◽  
Vol 111 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Bruce C. Frier ◽  
Chad R. Hancock ◽  
Jonathan P. Little ◽  
Natasha Fillmore ◽  
Tyler A. Bliss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Content ◽  
Mitochondrial Biogenesis ◽  
High Energy ◽  
Mitochondrial Enzymes ◽  
Mrna Levels ◽  
Rat Skeletal Muscle ◽  
Mitochondrial Content ◽  
Acute Bout

Receptor interacting protein 1 (RIP140) has recently been demonstrated to be a key player in the regulation of skeletal muscle mitochondrial content. We have shown that β-guanadinopropionic acid (β-GPA) feeding reduces RIP140 protein content and mRNA levels concomitant with increases in mitochondrial content (Williams DB, Sutherland LN, Bomhof MR, Basaraba SA, Thrush AB, Dyck DJ, Field CJ, Wright DC. Am J Physiol Endocrinol Metab 296: E1400–E1408, 2009). Since β-GPA feeding reduces high-energy phosphate levels and activates AMPK, alterations reminiscent of exercise, we hypothesized that exercise training would reduce RIP140 protein content. We further postulated that an acute bout of exercise, or interventions known to induce the expression of mitochondrial enzymes or genes involved in mitochondrial biogenesis, would result in decreases in nuclear RIP140 content. Two weeks of daily swim training increased markers of mitochondrial content in rat skeletal muscle independent of reductions in RIP140 protein. Similarly, high-intensity exercise training in humans failed to reduce RIP140 content despite increasing skeletal muscle mitochondrial enzymes. We found that 6 wk of daily 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) injections had no effect on RIP140 protein content in rat skeletal muscle while RIP140 content from LKB1 knockout mice was unaltered despite reductions in mitochondria. An acute bout of exercise, AICAR treatment, and epinephrine injections increased the mRNA levels of PGC-1α, COXIV, and lipin1 independent of decreases in nuclear RIP140 protein. Surprisingly these interventions increased RIP140 mRNA expression. In conclusion our results demonstrate that decreases in RIP140 protein content are not required for exercise and AMPK-dependent increases in skeletal muscle mitochondrial content, nor do acute perturbations alter the cellular localization of RIP140 in parallel with the induction of genes involved in mitochondrial biogenesis.

scholarly journals Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+channel gene expression

1999 ◽  
Vol 516 (2) ◽  
pp. 331-341 ◽  
Author(s):  
Zhong-Min Wang ◽  
María Laura Messi ◽  
Muthukrishnan Renganathan ◽  
Osvaldo Delbono
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Charge Movement ◽  
Insulin Like Growth Factor ◽  
Rat Skeletal Muscle ◽  
Channel Gene
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